PURPOSE: Transforming growth factor-β (TGF-β) induction of epithelial-mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27)...

Glaucoma is one of the leading causes of preventable blindness diseases, affecting more than 2 million people in the United States. Recently, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors were found to exert preventive effects against glaucoma. Therefore, we investigated whether carbenoxolone (CBX), an 11β-HSD1 inhibitor, prevents chemical ischemia-reperfusion-induced cell death in human trabecular meshwork (HTM) cells. The present study demonstrated that CBX inhibited cell death caused by iodoacetic acid (IAA)-induced ischemia-reperfusion, and its effect was associated with the inhibition of 11β-HSD1 expression and activity...

BACKGROUND: The major hallmark of Alzheimer's disease (AD) is the formation of amyloid aggregates, which are formed due to improper folding of proteins leading to the aggregation of amyloid beta (Aβ) 42 peptide. Inhibition of Aβ 42 aggregation using a drug such as carbenoxolone (Cbx), which has already been stated as neuroprotective, appears to be an effective approach against AD. OBJECTIVE: The present study was designed to investigate the anti-fibrillation activity of Cbx against the Aβ 42 aggregation...

OBJECTIVE: To investigate the effect of silver nanoparticles (AgNPs) on hemichannel activity in human skin keratinocytes (HaCaT) and to explore the role of hemichannel in AgNP-induced anti-proliferative effect on HaCaT cells. METHODS: HaCaT cells were exposed to 0, 0.1, 0.2, 1.0, 5.0, 10.0, 15.0 and 20.0 μg/cm(2) of AgNPs for 24 h and cell viability was assessed by propidium iodide (PI) staining with flow cytometry. Hemichannel activity was examined by ethidium bromide (EB) uptake experiments in cells exposed to AgNPs with and without hemichannel inhibitor carbenoxolone (CBX)...

Polycomb group (PcG) proteins form at least two key complexes, namely polycomb repressive complex 1 and polycomb repressive complex 2. These complexes are involved in the progression of various cancers. Systematic research has not been conducted on the aberrant expression of PcG members in gliomas. Using the Chinese Glioma Genome Atlas data set, PcG expression patterns between normal brain tissues and glioma samples were analyzed, and a PcG-based classifier was then developed using BRB Cox regression and risk-score model...

Polycomb group (PcG) complexes modify histones to silence tumor suppressor genes, which exhibit an important function in tumorigenesis and progression. The chromobox (Cbx) protein family is a critical component of PcG-mediated repression. Cbx2, a member of the Cbx protein family, is hypothesized to exhibit a vital role in breast cancer. In the present study, immunohistochemical analysis using tissue microarrays was performed to determine the levels of Cbx2 protein expression in breast cancer. The association between Cbx2 expression and the clinical features and prognosis of 455 breast cancer patients was analyzed...

The one-step conversion of aliphatic carboxylic acids to the corresponding nitriles has been accomplished via the merger of visible light mediated photoredox and cyanobenziodoxolones (CBX) reagents. The reaction proceeded in high yields with natural and non-natural α-amino and α-oxy acids, affording a broad scope of nitriles with excellent tolerance of the substituents in the α position. The direct cyanation of dipeptides and drug precursors was also achieved. The mechanism of the decarboxylative cyanation was investigated both computationally and experimentally and compared with the previously developed alkynylation reaction...

Although we previously reported that the self-renewal of leukemia-initiating cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by β-Arrestin1, a multiple-function protein, the cellular senescence is critical for LICs fate and leukemia progress, and worthy for further investigation. Here we found that depletion of β-Arrestin1 extended the population doubling time and the percentage of senile cells, the signatures of cellular senescence, of B-ALL LICs. Moreover, lack of β-Arrestin1 enhanced the expression of proteins (CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and B-ALL-LICs-derived leukemic mice...

Pannexins (Panx) are proteins that form functional single membrane channels, but they have not yet been described in dogs. The aim of the present study was to detect Panx1, Panx2 and Panx3 in frozen-thawed dog spermatozoa using flow cytometry and immunofluorescence analyses, evaluating the relationship of these proteins with propidium iodide (PI) in frozen-thawed spermatozoa. Fresh and frozen-thawed dog spermatozoa from eight dogs were preincubated with 3μM PI with or without 15μM carbenoxolone (CBX) or 1mM probenecid (PBD), two Panx channel inhibitors, and then incubated with rabbit anti-Panx1, anti-Panx2 and anti-Panx3 antibodies (1:200)...

BACKGROUND: Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized "reader" domains. Despite efforts to elucidate reader domain-PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions...

Carbenoxolone (CBX) is a clinically prescribed drug for the treatment of digestive ulcer and inflammation. It is also a widely used pharmacological inhibitor of several channels in basic research. Given that the overactivity of several channels, including those inhibitable by CBX, underlies bladder dysfunction, we tested the potential therapeutic application and mechanism of CBX in the treatment of voiding dysfunction. In a mouse model of cystitis induced by cyclophosphamide (CYP), CBX administration prevented the CYP-elicited increase in bladder weight, oedema, haemorrhage, and urothelial injury...

Heat stress (HS) may result in economic losses to pig producers across the USA and worldwide. Despite significant advancements in management practices, HS continues to be a challenge. In this study, an in-feed antibiotic (carbadox, CBX) and antibiotic alternatives ( [XPC], and [SGX] fermentation products) were evaluated in a standard pig starter diet as mitigations against the negative effects of HS in pigs. A total of 100 gilts were obtained at weaning (6.87 ± 0.82 kg BW, 19.36 ± 0.72 d of age) and randomly assigned to dietary treatments (2 rooms/treatment, 2 pens/room, 6 to 7 pigs/pen)...

In this study, we used the peristaltic crawling of Drosophila larvae as a model to study how motor patterns are regulated by central circuits. We built an experimental system that allows simultaneous application of optogenetics and calcium imaging to the isolated ventral nerve cord (VNC). We then investigated the effects of manipulating local activity of motor neurons (MNs) on fictive locomotion observed as waves of MN activity propagating along neuromeres. Optical inhibition of MNs with halorhodopsin3 (NpHR3) in a middle segment (A4, A5 or A6), but not other segments, dramatically decreased the frequency of the motor waves...

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL) is a multifunctional traditional Chinese medicine and has been widely used in the treatment of cardiovascular and cerebrovascular diseases. Numerous studies demonstrate that TXL is a novel neuroprotective drug, however, the mechanisms are largely unknown. AIM OF THE STUDY: we aimed to demonstrate the protective effect of TXL on cerebral ischemia/reperfusion (I/R) injury and provide the evidence for the involvement of Connexin 43/Calpain II/ Bax/Caspase-3 pathway in TXL-mediated neuroprotection...

Glioblastoma multiforme (GBM) lacks effective therapeutic options leaving patients with a survival time of approximately one year. Recently, the alteration of chromatin modulators has been implicated in the pathogenesis and chemoresistance of numerous cancers; in particular, the Polycomb Group Proteins have been shown to play a role in glioblastoma progression and maintenance [1-5]. In this study, we aimed to identify drug combinations that decrease GBM cell viability by combining small molecule inhibitors against the Polycomb family with two standard chemotherapies...

Extracellular potassium concentration, [K(+)]o, is a major determinant of neuronal excitability. In the healthy brain, [K(+)]o levels are tightly controlled. During seizures, [K(+)]o increases up to 15mM and is thought to cause seizures due to its depolarizing effect. Although astrocytes have been suggested to play a key role in the redistribution (or spatial buffering) of excess K(+) through Connexin-43 (Cx43)-based Gap Junctions (GJs), the relation between this dynamic regulatory process and seizure generation remains unknown...